Oral dosage forms (ODFs) of drugs have previously been surrounded by a coating that had properties different from the properties of the interior. For example, coated tablets were the subject of U.S. Pat. No. 5,914,132, within which the coating allowed delivery of the drug to the colon, with its particular chemical environment, rather than in an earlier part of the gastrointestinal tract with its different chemical environment, such as pH and enzymatic system.
Methods and apparatus for coating pharmaceuticals were disclosed in U.S. Pat. No. 4,497,847, which disclosed methods for applying the coating to the pharmaceutical via spraying or immersing in a centrifugal fluidized coating apparatus or a fluidized bed granulating coating apparatus. These coatings were intended to provide various controlled-release profiles. Most commonly the main interior part of the tablet was formed by compression of powder.
In these and similar patents, the drug was not especially toxic or hazardous, and the coating did not serve the purpose of isolating the toxic or hazardous substance from personnel who manufacture or handle the product. Therefore, no unusual handling or manufacturing precautions beyond those ordinarily employed in the pharmaceutical industry were necessitated due to the properties of the drug. Furthermore, the coating process was usually performed on finished tablets or pellets that had been manufactured by a separate process, and not concurrent with the manufacture of the pharmaceutical form. Therefore, the coating process itself did not circumvent the powder-mixing step during manufacture, in which airborne particulate matters could be generated. Airborne particulate matters of highly toxic or potent pharmaceuticals created problems for manufacturing personnel and non-patient personnel that required special handling procedures. These procedures have often been both ineffective and expensive.
Soft gelatin capsules have been used to deliver actives in dissolved, solubilized, or suspended forms. Soft gelatin capsules have the advantages of avoiding exposure to airborne hazardous particles as well as achieving better content uniformity than other solid dosage forms. However, migration of solute and the actives from the liquid phase to the gelatin shell have been a major drawback. Soft gelatin capsules were also not suitable for formulation of actives which require long release duration, since the capsule itself did not sustain drug release. Soft gelatin capsules have therefore not been used with a drug that was highly toxic, potent or otherwise hazardous.
Some pharmaceuticals, such as anti-cancer drugs, are highly toxic. For example, 9-nitrocamptothecin is used to treat pancreatic cancer, and yet is so toxic that companies are unwilling to manufacture it into solid dosage forms because of the exposure danger inherent in conventional manufacturing techniques. There are also other types of pharmaceutical actives, such as hormones, that are so potent that non-patient personnel must not be exposed to even small quantities of them. Thus, there is a need for manufacturing techniques and ODFs which are better suited to the handling, both during and after manufacture, of substances which are highly toxic or potent or otherwise hazardous to non-patients.
One attempt to address handling issues of toxic components during manufacturing of ODFs was disclosed in WO 94/09762. The active ingredient was in liquid form and was applied to the core of the ODF as a film coating, and which was optionally surrounded by an overcoating for further isolation. This manufacturing technique involved a substantial number of sequential manufacturing steps and could only incorporate the amount of drug that was contained in the one thin layer that the liquid coating formed around the central form. Drugs that had low solubility were thus precluded.
Three dimensional printing (3DP) techniques have been used to manufacture medical devices as disclosed in U.S. Pat. Nos. 5,490,962; 5,869,170; and 5,518,680. However, 3DP manufacturing of medical devices failed to overcome many of the post processing steps, such as applying a coating, that were found in conventional manufacturing. Additionally, 3DP manufacturing of medical devices required a final step of removing and dedusting the medical device from the loose unbound powder in the powder bed. Dedusting removed some powder particles at the surface of the medical device that were not securely bound to the main body of the product. Dedusting included agitation applied to the medical device to remove loose powder particles and partially bound particles. When manufacturing a medical device with a hazardous material, loose powder particles can be problematic to the manufacturer. Furthermore, varying dedusting techniques may result in variations in drug quantity.